Nimodipine-induced improved survival rate of facial motor neurons following intracranial transection of the facial nerve in the adult rat.

OBJECT Neuronal survival is an important factor in the achievement of functional restitution after peripheral nerve injuries. Intracranial tumors or trauma may cause patients to exhibit a temporary or permanent facial nerve palsy. Nimodipine, which acts as an antagonist to L-type voltage-gated calcium channels, has been shown to be neuroprotective in various lesion models of the central and peripheral nervous systems. The aim of the present study was to evaluate the effect of nimodipine on motor neuron survival in the facial motor nucleus following intracranial transection of the adult rat facial nerve. METHODS The facial nerve was cut intracranially in the posterior cranial fossa. Nimodipine was administered orally preoperatively for 3 days and postoperatively for up to 1 month, after which the number of neuronal profiles was quantified. The glial reaction was studied in the facial nucleus for up to 1 month by using immunocytochemical analysis. There was a significantly larger proportion of surviving motor neurons 1 month postinjury in animals treated with nimodipine (61+/-6.7%) in comparison with untreated animals (26.8+/-11.3%). Immunocytochemical analysis showed an increase in the amount of OX42 (microglia), ED1 (macrophages), and anti-glial fibrillary acidic protein (astrocytes) ipsilateral to the nerve injury; however, there was no difference between the two experimental groups of animals 2 to 28 days after surgery. CONCLUSIONS The authors propose a neuroprotective role for nimodipine, which may be useful as a "cranial nerve protective agent" following insults such as head injury or skull base surgery.

[1]  O. Guntinas-Lichius,et al.  Nimodipine maintains in vivo the increase in GFAP and enhances the astroglial ensheathment of surviving motoneurons in the rat following permanent target deprivation , 1997, Journal of neurocytology.

[2]  E. Stennert,et al.  Nimodipine accelerates axonal sprouting after surgical repair of rat facial nerve , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  D. Price,et al.  Ventral root avulsion: An experimental model of death of adult motor neurons , 1994, The Journal of comparative neurology.

[4]  D. Choi,et al.  The effect of NMDA, AMPA/kainate, and calcium channel antagonists on traumatic cortical neuronal injury in culture , 1994, Brain Research.

[5]  J. Hell,et al.  Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits , 1993, The Journal of cell biology.

[6]  M. Svensson,et al.  Infusion of cytosine‐arabinoside into the cerebrospinal fluid of the rat brain inhibits the microglial cell proliferation after hypoglossal nerve injury , 1993, Glia.

[7]  D. Giulian,et al.  Brain glia release factors with opposing actions upon neuronal survival , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  D. Giulian Reactive glia as rivals in regulating neuronal survival , 1993, Glia.

[9]  G. Vrbová,et al.  Dependence of postnatal motoneurones on their targets: review and hypothesis , 1992, Trends in Neurosciences.

[10]  E. Wendt,et al.  Divergent effects of astroglial and microglial secretions on neuron growth and survival , 1992, Experimental Neurology.

[11]  M. Svensson,et al.  Evidence for activation of the complement cascade in the hypoglossal nucleus following peripheral nerve injury , 1992, Journal of Neuroimmunology.

[12]  K. Boje,et al.  Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death , 1992, Brain Research.

[13]  D. McTavish,et al.  Nimodipine. A review of its pharmacological properties, and therapeutic efficacy in cerebral disorders. , 1992, Drugs & aging.

[14]  W. Streit,et al.  MK‐801 prevents microglial reaction in rat hippocampus after forebrain ischemia , 1992, Neuroreport.

[15]  C. Théry,et al.  Cytotoxic Effect of Brain Macrophages on Developing Neurons , 1991, The European journal of neuroscience.

[16]  M. Passafaro,et al.  Physiopathology of neuronal voltage‐operated calcium channels , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  A. F. Esser Big MAC attack: complement proteins cause leaky patches. , 1991, Immunology today.

[18]  W. Gispen,et al.  Putative neurotrophic factors and functional recovery from peripheral nerve damage in the rat , 1991, British journal of pharmacology.

[19]  C. Slater,et al.  The effect of age on motor neurone death following axotomy in the mouse. , 1991, Development.

[20]  D. Attwell,et al.  The release and uptake of excitatory amino acids. , 1990, Trends in pharmacological sciences.

[21]  W. Catterall,et al.  Subunit structure and localization of dihydropyridine-sensitive calcium channels in mammalian brain, spinal cord, and retina , 1990, Neuron.

[22]  M. Reivich,et al.  Nimodipine attenuates both increase in cytosolic free calcium and histologic damage following focal cerebral ischemia and reperfusion in cats. , 1989, Stroke.

[23]  J. Traber,et al.  Pharmacological basis for the use of nimodipine in central nervous system disorders , 1989, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[24]  D. Choi Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage , 1988, Trends in Neurosciences.

[25]  H. J. G. Gundersen,et al.  The new stereological tools: Disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis , 1988, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[26]  G. Kreutzberg,et al.  Response of endogenous glial cells to motor neuron degeneration induced by toxic ricin , 1988, The Journal of comparative neurology.

[27]  W. Gispen,et al.  Oral administration of nimodipine accelerates functional recovery following peripheral nerve damage in the rat , 1987, Neuroscience Letters.

[28]  D. Choi,et al.  Dextrorphan and levorphanol selectively block N-methyl-D-aspartate receptor-mediated neurotoxicity on cortical neurons. , 1987, The Journal of pharmacology and experimental therapeutics.

[29]  G. Foster,et al.  [H3]-nitrendipine binding in non-neuronal cell cultures. , 1986, Biochemical and biophysical research communications.

[30]  H. Schmalbruch,et al.  Motoneuron death after sciatic nerve section in newborn rats , 1984, The Journal of comparative neurology.

[31]  A Grinvald,et al.  Localization of voltage-sensitive calcium channels along developing neurites: their possible role in regulating neurite elongation. , 1982, Developmental biology.

[32]  H. Aldskogius GLIAL CELL RESPONSES IN THE ADULT RABBIT DORSAL MOTOR VAGAL NUCLEUS DURING AXON REACTION , 1982, Neuropathology and applied neurobiology.

[33]  H. Thoenen,et al.  Physiology of nerve growth factor. , 1980, Physiological reviews.

[34]  J. Farber,et al.  Calcium dependence of toxic cell death: a final common pathway. , 1979, Science.

[35]  C. P. Leblond,et al.  Investigation of glial cells in semithin sections. I. Identification of glial cells in the brain of young rats , 1973, The Journal of comparative neurology.

[36]  M. Abercrombie Estimation of nuclear population from microtome sections , 1946, The Anatomical record.

[37]  A. Gunkel,et al.  Nimodipine-accelerated hypoglossal sprouting prevents the postoperative hyperinnervation of target muscles after hypo glossal-facial anastomosis in the rat. , 1997, Restorative neurology and neuroscience.

[38]  P. Mattsson,et al.  Evidence for activation of the terminal pathway of complement and upregulation of sulfated glycoprotein (SGP)-2 in the hypoglossal nucleus following peripheral nerve injury. , 1995, Molecular and chemical neuropathology.

[39]  B. Morgan Effects of the membrane attack complex of complement on nucleated cells. , 1992, Current topics in microbiology and immunology.

[40]  W. Gispen,et al.  CNS and PNS effects of nimodipine. , 1990, Journal of neural transmission. Supplementum.

[41]  A. Søreide Variations in the axon reaction after different types of nerve lesion. Light and electron microscopic studies on the facial nucleus of the rat. , 1981, Acta anatomica.